title: Requirements for eomesodermin and promyelocytic leukemia zinc finger in the development of innate-like CD8+ T cells.
abstract: Conventional and nonconventional T cell development occur in the thymus. Nonconventional thymocytes that bear characteristics typically associated with innate immune cells are termed innate-like lymphocytes (ILLs). Mice harboring a tyrosine to phenylalanine mutation in the adaptor protein Src homology 2 domain-containing leukocyte protein of 76 kDa at residue 145 (Y145F mice) develop an expanded population of CD8(+)CD122(+)CD44(+) ILLs, typified by expression of the T-box transcription factor eomesodermin. Y145F mice also have an expanded population of γδ T cells that produce copious amounts of IL-4 via a mechanism that is dependent on the BTB-ZF transcription factor promyelocytic leukemia zinc finger. Using mice with T cell-specific deletion of Eomes, we demonstrate that this transcription factor is required for CD8(+) ILL development in Y145F as well as wild-type mice. Moreover, we show that promyelocytic leukemia zinc finger and IL-4 are also required for the generation of this ILL population. Taken together, these data shed light on the cell-intrinsic and cell-extrinsic factors that drive CD8(+) ILL differentiation.
authors.affiliation: Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Gordon
authors.forename: Shannon A
authors.initials: SA
authors.lastname: Carty
authors.forename: Jiyeon S
authors.initials: JS
authors.lastname: Kim
authors.forename: Tao
authors.initials: T
authors.lastname: Zou
authors.forename: Jennifer
authors.initials: J
authors.lastname: Smith-Garvin
authors.forename: Eric S
authors.initials: ES
authors.lastname: Alonzo
authors.forename: Ethan
authors.initials: E
authors.lastname: Haimm
authors.forename: Derek B
authors.initials: DB
authors.lastname: Sant'Angelo
authors.forename: Gary A
authors.initials: GA
authors.lastname: Koretzky
authors.forename: Steven L
authors.initials: SL
authors.lastname: Reiner
authors.forename: Martha S
authors.initials: MS
authors.lastname: Jordan
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology*; D019943:Amino Acid Substitution; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D010750:Phosphoproteins / Q000235:genetics / Q000276:immunology*; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D020825:T-Box Domain Proteins / Q000235:genetics / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016335:Zinc Fingers / Q000235:genetics / Q000276:immunology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C491198:Eomes protein, mouse; D051741:Kruppel-Like Transcription Factors; D010750:Phosphoproteins; D000075722:Promyelocytic Leukemia Zinc Finger Protein; C092947:SLP-76 signal Transducing adaptor proteins; D020825:T-Box Domain Proteins; C513267:Zbtb16 protein, mouse; D015847:Interleukin-4; D007371:Interferon-gamma